RRC ID 52547
Author Kumagai M, Watanabe A, Yoshida I, Mishima T, Nakamura M, Nishikawa K, Morimoto Y.
Title Evaluation of Aculeatin and Toddaculin Isolated from Toddalia asiatica as Anti-inflammatory Agents in LPS-Stimulated RAW264 Macrophages.
Journal Biol Pharm Bull
Abstract Anti-inflammatory activity of aculeatin and toddaculin, which are coumarins with a similar structure isolated from Toddalia asiatica (L.) LAM., was evaluated using lipopolysaccharide (LPS)-stimulated RAW264 mouse macrophage cells. Both aculeatin and toddaculin significantly inhibited mRNA expression of inflammatory mediators and nitric oxide production. Furthermore, Toddaculin suppressed LPS-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 and inhibited LPS-induced activation of nuclear factor-kappaB (NF-κB). However, aculeatin did not exhibit such effects, suggesting that aculeatin and toddaculin suppress LPS-induced inflammation of RAW264 cells via different mechanisms. The cellular uptake of these compounds was also evaluated. Toddaculin was detected in RAW264 cells after 4 and 24 h. However, aculeatin levels were not observed in RAW264 cells at all incubation intervals. These results indicate that de-epoxidation of a prenyl group can increase hydrophobicity of molecule and is thought to accelerate cellular uptake and/or interactions with the phospholipid bilayers of cell membranes.
Volume 41(1)
Pages 132-137
Published 2018
DOI 10.1248/bpb.b17-00607
PMID 29311475
MeSH Animals Anti-Inflammatory Agents / isolation & purification Anti-Inflammatory Agents / metabolism Anti-Inflammatory Agents / pharmacology* Cell Line Cell Survival / drug effects Coumarins / isolation & purification Coumarins / metabolism Coumarins / pharmacology* Cytokines / biosynthesis Lipopolysaccharides / pharmacology Macrophages / drug effects* Macrophages / immunology Macrophages / metabolism Mice Molecular Structure Nitric Oxide / biosynthesis Rutaceae / chemistry*
IF 1.54
Times Cited 3
Human and Animal Cells RAW 264(RCB0535)